Cancer (neoplasia) is characterized by deregulated cell growth and cell division. There are numerous types of cancers. As one example, prostate cancer, as its name indicates, is a cancer that develops in the prostate gland of the male reproductive system. Prostate cancer can be aggressive, in which cancer cells metastasize and move from the prostate gland to other parts of the body, such as the lymph nodes and the bones. It is the second leading cause of cancer-related death in men in the US, and its prevalence is increasing in developing countries.
More than 200,000 new cases of prostate cancer are diagnosed in the US each year. Of these, roughly 88% or 176,000 have localized disease that can be treated with surgery, radiation, cryotherapy or watchful waiting.
Prostate cancer growth is often driven by male sex hormones called androgens, which include testosterone. Because of this, a common treatment option for the 22% or 35,200 patients that cannot be treated with surgery, radiation, cryotherapy or watchful waiting is to lower the levels of androgens in the man's body. Androgen levels can be lowered by surgically removing the testicles or with drugs that stop the testicles, and to a lesser extent adrenal glands, from making androgens or block how they affect the body. This type of treatment is called hormone therapy or androgen-deprivation therapy.
Unfortunately, about 40,000 patients each year begin to fail hormone therapy or become hormone refractory. That is, they develop castration-resistant prostate cancer (CRPC) or hormone refractory prostate cancer (HRPC).
Treatment options for prostate cancer are very limited once the disease becomes resistant to hormonal therapy. In the past few years, docetaxel was the only treatment option for patients with CRPC.
Recently, the FDA approved a chemotherapeutic drug, cabazitaxel, for clinical management of CRPC. Cabazitaxel has shown survival benefits for patients with CRPC. The drug is used to treat men with advanced prostate cancer after treatment with other anticancer agents, including docetaxel, have failed to curtail cancer progression. Thus, cabazitaxel is mostly administered to patients when docetaxel is no longer effective.
Although cabazitaxel has been shown to increase the overall survival of prostate cancer patients, it has serious adverse side effects. These include low white blood cell count, low red blood cell count, low blood platelet count, nausea, vomiting, constipation and diarrhea, and decreased appetite, shortness of breath, tiredness and hair loss.
Galeterone also named TOK-001 or VN/124-1, is a small molecule, oral drug that is capable of disrupting androgen receptor signaling. In preclinical studies, Galeterone has been shown to selectively inhibit cytochrome C17α-hydroxylase/C17-20-lyase (CYP17) lyase to prevent biosynthesis of androgens, antagonize testosterone binding to the androgen receptor (AR), and degrade the AR protein. Galeterone is the first drug in development that has been shown to have all three properties. At the time of this application's filing, Galeterone is undergoing a Phase III clinical trial for the treatment of metastatic CRPC.